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Bone & Joint Research
Vol. 13, Issue 7 | Pages 321 - 331
3 Jul 2024
Naito T Yamanaka Y Tokuda K Sato N Tajima T Tsukamoto M Suzuki H Kawasaki M Nakamura E Sakai A

Aims. The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice. Methods. Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro. Results. The expression of all fibrosis-related genes was higher in Db met(-) than in WT met(-) and was suppressed by metformin. Increased levels of fibrosis-related genes, posterior capsule thickness, and collagen density were observed in the capsules of db/db mice compared with those in WT mice; these effects were suppressed by metformin. Glucose addition increased fibrosis-related gene expression in both groups of mice in vitro. When glucose was added, metformin inhibited the expression of fibrosis-related genes other than cellular communication network factor 2 (Ccn2) in WT mouse cells. Conclusion. Hyperglycaemia promotes fibrosis in the mouse knee joint capsule, which is inhibited by metformin. These findings can help inform the development of novel strategies for treating knee joint capsule fibrosis. Cite this article: Bone Joint Res 2024;13(7):321–331


Bone & Joint Open
Vol. 5, Issue 7 | Pages 534 - 542
1 Jul 2024
Woods A Howard A Peckham N Rombach I Saleh A Achten J Appelbe D Thamattore P Gwilym SE

Aims

The primary aim of this study was to assess the feasibility of recruiting and retaining patients to a patient-blinded randomized controlled trial comparing corticosteroid injection (CSI) to autologous protein solution (APS) injection for the treatment of subacromial shoulder pain in a community care setting. The study focused on recruitment rates and retention of participants throughout, and collected data on the interventions’ safety and efficacy.

Methods

Participants were recruited from two community musculoskeletal treatment centres in the UK. Patients were eligible if aged 18 years or older, and had a clinical diagnosis of subacromial impingement syndrome which the treating clinician thought was suitable for treatment with a subacromial injection. Consenting patients were randomly allocated 1:1 to a patient-blinded subacromial injection of CSI (standard care) or APS. The primary outcome measures of this study relate to rates of recruitment, retention, and compliance with intervention and follow-up to determine feasibility. Secondary outcome measures relate to the safety and efficacy of the interventions.


Bone & Joint Open
Vol. 5, Issue 4 | Pages 361 - 366
24 Apr 2024
Shafi SQ Yoshimura R Harrison CJ Wade RG Shaw AV Totty JP Rodrigues JN Gardiner MD Wormald JCR

Aims

Hand trauma, consisting of injuries to both the hand and the wrist, are a common injury seen worldwide. The global age-standardized incidence of hand trauma exceeds 179 per 100,000. Hand trauma may require surgical management and therefore result in significant costs to both healthcare systems and society. Surgical site infections (SSIs) are common following all surgical interventions, and within hand surgery the risk of SSI is at least 5%. SSI following hand trauma surgery results in significant costs to healthcare systems with estimations of over £450 per patient. The World Health Organization (WHO) have produced international guidelines to help prevent SSIs. However, it is unclear what variability exists in the adherence to these guidelines within hand trauma. The aim is to assess compliance to the WHO global guidelines in prevention of SSI in hand trauma.

Methods

This will be an international, multicentre audit comparing antimicrobial practices in hand trauma to the standards outlined by WHO. Through the Reconstructive Surgery Trials Network (RSTN), hand surgeons across the globe will be invited to participate in the study. Consultant surgeons/associate specialists managing hand trauma and members of the multidisciplinary team will be identified at participating sites. Teams will be asked to collect data prospectively on a minimum of 20 consecutive patients. The audit will run for eight months. Data collected will include injury details, initial management, hand trauma team management, operation details, postoperative care, and antimicrobial techniques used throughout. Adherence to WHO global guidelines for SSI will be summarized using descriptive statistics across each criteria.


Bone & Joint Open
Vol. 5, Issue 3 | Pages 162 - 173
4 Mar 2024
Di Mascio L Hamborg T Mihaylova B Kassam J Shah B Stuart B Griffin XL

Aims

Is it feasible to conduct a definitive multicentre trial in community settings of corticosteroid injections (CSI) and hydrodilation (HD) compared to CSI for patients with frozen shoulder? An adequately powered definitive randomized controlled trial (RCT) delivered in primary care will inform clinicians and the public whether hydrodilation is a clinically and cost-effective intervention. In this study, prior to a full RCT, we propose a feasibility trial to evaluate recruitment and retention by patient and clinician willingness of randomization; rates of withdrawal, crossover and attrition; and feasibility of outcome data collection from routine primary and secondary care data.

Methods

In the UK, the National Institute for Health and Care Excellence (NICE) advises that prompt early management of frozen shoulder is initiated in primary care settings with analgesia, physiotherapy, and joint injections; most people can be managed without an operation. Currently, there is variation in the type of joint injection: 1) CSI, thought to reduce the inflammation of the capsule reducing pain; and 2) HD, where a small volume of fluid is injected into the shoulder joint along with the steroid, aiming to stretch the capsule of the shoulder to improve pain, but also allowing greater movement. The creation of musculoskeletal hubs nationwide provides infrastructure for the early and effective management of frozen shoulder. This potentially reduces costs to individuals and the wider NHS perhaps negating the need for a secondary care referral.


Bone & Joint Open
Vol. 4, Issue 10 | Pages 801 - 807
23 Oct 2023
Walter N Szymski D Kurtz SM Lowenberg DW Alt V Lau EC Rupp M

Aims

This work aimed at answering the following research questions: 1) What is the rate of mechanical complications, nonunion and infection for head/neck femoral fractures, intertrochanteric fractures, and subtrochanteric fractures in the elderly USA population? and 2) Which factors influence adverse outcomes?

Methods

Proximal femoral fractures occurred between 1 January 2009 and 31 December 2019 were identified from the Medicare Physician Service Records Data Base. The Kaplan-Meier method with Fine and Gray sub-distribution adaptation was used to determine rates for nonunion, infection, and mechanical complications. Semiparametric Cox regression model was applied incorporating 23 measures as covariates to identify risk factors.


Bone & Joint Research
Vol. 12, Issue 10 | Pages 657 - 666
17 Oct 2023
Sung J Barratt KR Pederson SM Chenu C Reichert I Atkins GJ Anderson PH Smitham PJ

Aims. Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy. Methods. Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq). Results. Radiographs and histology demonstrated impaired fracture healing in ZDF rats with incomplete bony bridge formation and an influx of intramedullary inflammatory tissue. In comparison, near-complete bridging between cortices was observed in Sham WT animals. Of 13,160 genes, mRNA-Seq analysis identified 13 that were differentially expressed in ZDF rat callus, using a false discovery rate (FDR) threshold of 10%. Seven genes were upregulated with high confidence (FDR = 0.05) in ZDF fracture callus, most with known roles in inflammation. Conclusion. These findings suggest that elevated or prolonged inflammation contributes to delayed fracture healing in T2DM. The identified genes may be used as biomarkers to monitor and treat delayed fracture healing in diabetic patients. Cite this article: Bone Joint Res 2023;12(10):657–666


Bone & Joint Research
Vol. 12, Issue 9 | Pages 522 - 535
4 Sep 2023
Zhang G Li L Luo Z Zhang C Wang Y Kang X

Aims

This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

Methods

The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions.


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 795 - 800
1 Jul 2023
Parsons N Achten J Costa ML

Aims

To report the outcomes of patients with a fracture of the distal tibia who were treated with intramedullary nail versus locking plate in the five years after participating in the Fixation of Distal Tibia fracture (FixDT) trial.

Methods

The FixDT trial reported the results for 321 patients randomized to nail or locking plate fixation in the first 12 months after their injury. In this follow-up study, we report the results of 170 of the original participants who agreed to be followed up until five years. Participants reported their Disability Rating Index (DRI) and health-related quality of life (EuroQol five-dimension three-level questionnaire) annually by self-reported questionnaire. Further surgical interventions related to the fracture were also recorded.


Bone & Joint Open
Vol. 4, Issue 6 | Pages 442 - 446
12 Jun 2023
Toda Y Iwata S Kobayashi E Ogura K Osaki S Fukushima S Mawatari M Kawai A

Aims

The risk of postoperative complications after resection of soft-tissue sarcoma in the medial thigh is higher than in other locations. This study investigated whether a vessel sealing system (VSS) could help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh.

Methods

Of 285 patients who underwent wide resection for soft-tissue sarcoma between 2014 and 2021 at our institution, 78 patients with tumours in the medial thigh were extracted from our database. Information on clinicopathological characteristics, preoperative treatment, surgical treatment (use of VSS, blood loss volume, operating time), and postoperative course (complications, postoperative haemoglobin changes, total drainage volume, and drainage and hospitalization durations) were obtained from medical records. We statistically compared clinical outcomes between patients whose surgery did or did not use VSS (VSS and non-VSS groups, respectively).


Bone & Joint Open
Vol. 4, Issue 3 | Pages 205 - 209
16 Mar 2023
Jump CM Mati W Maley A Taylor R Gratrix K Blundell C Lane S Solanki N Khan M Choudhry M Shetty V Malik RA Charalambous CP

Aims

Frozen shoulder is a common, painful condition that results in impairment of function. Corticosteroid injections are commonly used for frozen shoulder and can be given as glenohumeral joint (GHJ) injection or suprascapular nerve block (SSNB). Both injection types have been shown to significantly improve shoulder pain and range of motion. It is not currently known which is superior in terms of relieving patients’ symptoms. This is the protocol for a randomized clinical trial to investigate the clinical effectiveness of corticosteroid injection given as either a GHJ injection or SSNB.

Methods

The Therapeutic Injections For Frozen Shoulder (TIFFS) study is a single centre, parallel, two-arm, randomized clinical trial. Participants will be allocated on a 1:1 basis to either a GHJ corticosteroid injection or SSNB. Participants in both trial arms will then receive physiotherapy as normal for frozen shoulder. The primary analysis will compare the Oxford Shoulder Score (OSS) at three months after injection. Secondary outcomes include OSS at six and 12 months, range of shoulder movement at three months, and Numeric Pain Rating Scale, abbreviated Disabilities of Arm, Shoulder and Hand score, and EuroQol five-level five-dimension health index at three months, six months, and one year after injection. A minimum of 40 patients will be recruited to obtain 80% power to detect a minimally important difference of ten points on the OSS between the groups at three months after injection. The study is registered under ClinicalTrials.gov with the identifier NCT04965376.


Bone & Joint Open
Vol. 4, Issue 3 | Pages 146 - 157
7 Mar 2023
Camilleri-Brennan J James S McDaid C Adamson J Jones K O'Carroll G Akhter Z Eltayeb M Sharma H

Aims

Chronic osteomyelitis (COM) of the lower limb in adults can be surgically managed by either limb reconstruction or amputation. This scoping review aims to map the outcomes used in studies surgically managing COM in order to aid future development of a core outcome set.

Methods

A total of 11 databases were searched. A subset of studies published between 1 October 2020 and 1 January 2011 from a larger review mapping research on limb reconstruction and limb amputation for the management of lower limb COM were eligible. All outcomes were extracted and recorded verbatim. Outcomes were grouped and categorized as per the revised Williamson and Clarke taxonomy.


Bone & Joint Open
Vol. 4, Issue 2 | Pages 96 - 103
14 Feb 2023
Knowlson CN Brealey S Keding A Torgerson D Rangan A

Aims

Early large treatment effects can arise in small studies, which lessen as more data accumulate. This study aimed to retrospectively examine whether early treatment effects occurred for two multicentre orthopaedic randomized controlled trials (RCTs) and explore biases related to this.

Methods

Included RCTs were ProFHER (PROximal Fracture of the Humerus: Evaluation by Randomisation), a two-arm study of surgery versus non-surgical treatment for proximal humerus fractures, and UK FROST (United Kingdom Frozen Shoulder Trial), a three-arm study of two surgical and one non-surgical treatment for frozen shoulder. To determine whether early treatment effects were present, the primary outcome of Oxford Shoulder Score (OSS) was compared on forest plots for: the chief investigator’s (CI) site to the remaining sites, the first five sites opened to the other sites, and patients grouped in quintiles by randomization date. Potential for bias was assessed by comparing mean age and proportion of patients with indicators of poor outcome between included and excluded/non-consenting participants.


Bone & Joint Research
Vol. 12, Issue 2 | Pages 103 - 112
1 Feb 2023
Walter N Szymski D Kurtz SM Lowenberg DW Alt V Lau E Rupp M

Aims

The optimal choice of management for proximal humerus fractures (PHFs) has been increasingly discussed in the literature, and this work aimed to answer the following questions: 1) what are the incidence rates of PHF in the geriatric population in the USA; 2) what is the mortality rate after PHF in the elderly population, specifically for distinct treatment procedures; and 3) what factors influence the mortality rate?

Methods

PHFs occurring between 1 January 2009 and 31 December 2019 were identified from the Medicare physician service records. Incidence rates were determined, mortality rates were calculated, and semiparametric Cox regression was applied, incorporating 23 demographic, clinical, and socioeconomic covariates, to compare the mortality risk between treatments.


Bone & Joint Research
Vol. 11, Issue 10 | Pages 700 - 714
4 Oct 2022
Li J Cheung W Chow SK Ip M Leung SYS Wong RMY

Aims

Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

Methods

Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted.


Bone & Joint Open
Vol. 3, Issue 10 | Pages 746 - 752
1 Oct 2022
Hadfield JN Omogbehin TS Brookes C Walker R Trompeter A Bretherton CP Gray A Eardley WGP

Aims. Understanding of open fracture management is skewed due to reliance on small-number lower limb, specialist unit reports and large, unfocused registry data collections. To address this, we carried out the Open Fracture Patient Evaluation Nationwide (OPEN) study, and report the demographic details and the initial steps of care for patients admitted with open fractures in the UK. Methods. Any patient admitted to hospital with an open fracture between 1 June 2021 and 30 September 2021 was included, excluding phalanges and isolated hand injuries. Institutional information governance approval was obtained at the lead site and all data entered using Research Electronic Data Capture. Demographic details, injury, fracture classification, and patient dispersal were detailed. Results. In total, 1,175 patients (median age 47 years (interquartile range (IQR) 29 to 65), 61.0% male (n = 717)) were admitted across 51 sites. A total of 546 patients (47.1%) were employed, 5.4% (n = 63) were diabetic, and 28.8% (n = 335) were smokers. In total, 29.0% of patients (n = 341) had more than one injury and 4.8% (n = 56) had two or more open fractures, while 51.3% of fractures (n = 637) occurred in the lower leg. Fractures sustained in vehicle incidents and collisions are common (38.8%; n = 455) and typically seen in younger patients. A simple fall (35.0%; n = 410) is common in older people. Overall, 69.8% (n = 786) of patients were admitted directly to an orthoplastic centre, 23.0% (n = 259) were transferred to an orthoplastic centre after initial management elsewhere, and 7.2% were managed outwith specialist units (n = 81). Conclusion. This study describes the epidemiology of open fractures in the UK. For a decade, orthopaedic surgeons have been practicing in a guideline-driven, network system without understanding the patient features, injury characteristics, or dispersal processes of the wider population. This work will inform care pathways as the UK looks to the future of trauma networks and guidelines, and how to optimize care for patients with open fractures. Cite this article: Bone Jt Open 2022;3(10):746–752


Bone & Joint Open
Vol. 3, Issue 9 | Pages 684 - 691
1 Sep 2022
Rodriguez S Shen TS Lebrun DG Della Valle AG Ast MP Rodriguez JA

Aims

The volume of ambulatory total hip arthroplasty (THA) procedures is increasing due to the emphasis on value-based care. The purpose of the study is to identify the causes for failed same-day discharge (SDD) and perioperative factors leading to failed SDD.

Methods

This retrospective cohort study followed pre-selected patients for SDD THA from 1 August 2018 to 31 December 2020. Inclusion criteria were patients undergoing unilateral THA with appropriate social support, age 18 to 75 years, and BMI < 37 kg/m2. Patients with opioid dependence, coronary artery disease, and valvular heart disease were excluded. Demographics, comorbidities, and perioperative data were collected from the electronic medical records. Possible risk factors for failed SDD were identified using multivariate logistic regression.


Bone & Joint Open
Vol. 3, Issue 8 | Pages 618 - 622
1 Aug 2022
Robinson AHN Garg P Kirmani S Allen P

Aims

Diabetic foot care is a significant burden on the NHS in England. We have conducted a nationwide survey to determine the current participation of orthopaedic surgeons in diabetic foot care in England.

Methods

A questionnaire was sent to all 136 NHS trusts audited in the 2018 National Diabetic Foot Audit (NDFA). The questionnaire asked about the structure of diabetic foot care services.


Bone & Joint Research
Vol. 11, Issue 5 | Pages 292 - 300
13 May 2022
He C Chen C Jiang X Li H Zhu L Wang P Xiao T

Osteoarthritis (OA) is a degenerative disease resulting from progressive joint destruction caused by many factors. Its pathogenesis is complex and has not been elucidated to date. Advanced glycation end products (AGEs) are a series of irreversible and stable macromolecular complexes formed by reducing sugar with protein, lipid, and nucleic acid through a non-enzymatic glycosylation reaction (Maillard reaction). They are an important indicator of the degree of ageing. Currently, it is considered that AGEs accumulation in vivo is a molecular basis of age-induced OA, and AGEs production and accumulation in vivo is one of the important reasons for the induction and acceleration of the pathological changes of OA. In recent years, it has been found that AGEs are involved in a variety of pathological processes of OA, including extracellular matrix degradation, chondrocyte apoptosis, and autophagy. Clearly, AGEs play an important role in regulating the expression of OA-related genes and maintaining the chondrocyte phenotype and the stability of the intra-articular environment. This article reviews the latest research results of AGEs in a variety of pathological processes of OA, to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment.

Cite this article: Bone Joint Res 2022;11(5):292–300.


Bone & Joint Open
Vol. 3, Issue 4 | Pages 340 - 347
22 Apr 2022
Winkler T Costa ML Ofir R Parolini O Geissler S Volk H Eder C

Aims

The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells.

Methods

HIPGEN is a multicentre, multinational, randomized, double-blind, placebo-controlled trial. A total of 240 patients aged 60 to 90 years with low-energy femoral neck fractures (FNF) will be allocated to two arms and receive an intramuscular injection of either 150 × 106 PLX-PAD cells or placebo into the medial gluteal muscle after direct lateral implantation of total or hemi hip arthroplasty. Patients will be followed for two years. The primary endpoint is the Short Physical Performance Battery (SPPB) at week 26. Secondary and exploratory endpoints include morphological parameters (lean body mass), functional parameters (abduction and handgrip strength, symmetry in gait, weightbearing), all-cause mortality rate and patient-reported outcome measures (Lower Limb Measure, EuroQol five-dimension questionnaire). Immunological biomarker and in vitro studies will be performed to analyze the PLX-PAD mechanism of action. A sample size of 240 subjects was calculated providing 88% power for the detection of a 1 SPPB point treatment effect for a two-sided test with an α level of 5%.


Bone & Joint Research
Vol. 11, Issue 4 | Pages 189 - 199
13 Apr 2022
Yang Y Li Y Pan Q Bai S Wang H Pan X Ling K Li G

Aims

Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model.

Methods

A novel rat model of TTT was established with a designed external fixator, and effects on wound healing were investigated. Laser speckle perfusion imaging, vessel perfusion, histology, and immunohistochemistry were used to evaluate the wound healing processes.